HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Medana, I. Articles by Neumann, H. Search for Related Content PubMed PubMed Citation Articles by Medana, I. Articles by Neumann, H.

Fas Ligand (CD95L) Protects Neurons Against Perforin- Mediated T Lymphocyte Cytotoxicity¹

Isabelle Medana^*, Zhaoxia Li^*, Alexander Flügel^*, Jürg Tschopp, Hartmut Wekerle^* and Harald Neumann^2,*

^* Department of Neuroimmunology, Max-Planck Institute of Neurobiology, Martinsried, Germany; and Institut de Biochimie, University of Lausanne, Epalinges, Switzerland

Previous work showed that neurons of the CNS are protected against perforin-mediated T cell cytotoxicity, but are susceptible to Fas-mediated apoptosis. In this study, we report that Fas ligand (FasL) expression by neurons is involved in protection against perforin-mediated T cell cytotoxicity. Gene transcripts for FasL were identified in single murine hippocampal neurons by RT-PCR combined with patch clamp electrophysiology, and constitutive expression of FasL protein was confirmed in neurons by immunohistochemistry. Neurons derived from wild-type C57BL/6 (BL6) mice and mutant BL6.gld mice lacking functional FasL were confronted with allogeneic CTLs and continuously monitored in real time for changes in levels of intracellular calcium ([Ca²⁺]_i), an indicator of cytotoxic damage. Perforin-mediated plasma membrane lysis, characterized by rapid, massive [Ca²⁺]_i influx into the target cells within 0.5 h, was not detected in wild-type neurons. In striking contrast, FasL-deficient neurons showed rapid increase in [Ca²⁺]_i within 0.5 h, reflecting perforin-dependent cell lysis. FasL seems to protect neurons by blocking degranulation of CTLs, since CD3-induced release of cytotoxic granules was reduced by coapplication of Fas-specific Abs or rFasL.

This article has been cited by other articles:

				E. K. Mathey, T. Derfuss, M. K. Storch, K. R. Williams, K. Hales, D. R. Woolley, A. Al-Hayani, S. N. Davies, M. N. Rasband, T. Olsson, et al. Neurofascin as a novel target for autoantibody-mediated axonal injury J. Exp. Med., October 1, 2007; 204(10): 2363 - 2372. [Abstract] [Full Text] [PDF]

				G. Brunlid, J. Pruszak, B. Holmes, O. Isacson, and K.-C. Sonntag Immature and Neurally Differentiated Mouse Embryonic Stem Cells Do Not Express a Functional Fas/Fas Ligand System Stem Cells, October 1, 2007; 25(10): 2551 - 2558. [Abstract] [Full Text] [PDF]

				V. W. Yong, F. Giuliani, M. Xue, A. Bar-Or, and L. M. Metz Experimental models of neuroprotection relevant to multiple sclerosis Neurology, May 29, 2007; 68(22_suppl_3): S32 - S37. [Abstract] [Full Text] [PDF]

				R P Lisak, J A Benjamins, B Bealmear, B Yao, S Land, L Nedelkoska, and D Skundric Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for immune-related molecules by central nervous system mixed glial cell cultures Multiple Sclerosis, April 1, 2006; 12(2): 149 - 168. [Abstract] [PDF]

				Y. Zhu, J. Antony, S. Liu, J. A. Martinez, F. Giuliani, D. Zochodne, and C. Power CD8+ lymphocyte-mediated injury of dorsal root ganglion neurons during lentivirus infection: CD154-dependent cell contact neurotoxicity. J. Neurosci., March 29, 2006; 26(13): 3396 - 3403. [Abstract] [Full Text] [PDF]

				M. Lafon, C. Prehaud, F. Megret, M. Lafage, G. Mouillot, M. Roa, P. Moreau, N. Rouas-Freiss, and E. D. Carosella Modulation of HLA-G Expression in Human Neural Cells after Neurotropic Viral Infections J. Virol., December 15, 2005; 79(24): 15226 - 15237. [Abstract] [Full Text] [PDF]